Studies the coming year will focus on the early permeability change in the esophageal epithelium with acid damage and on a correlation of esophageal P. D., histology, and clinical course in patients with reflux exophagitis. The magnitude and permselectivity of the extracellular passive permeation route of the rabbit esophagus will be measured in vitro by determining diffusion potentials and the rates of passive transfer of 22Na, 36C1, 14C-mannitol and 140lanthanum in esophagi with varying degrees of acid damage. The location of this route will be studied by electron microscopy of the tissue sections following the physiological studies with the electron dense markers. To correlate changes in human disease with P. D. measurements, two kinds of studies are proposed. First, sodium and chloride transport will be measured in vitro in normal esophageal mucosa from the margins of human esophagi recorded for carcinoma. Such measurements will determine the orgin of the transmucosal P. D. in the human esophagus. Secondly, patients with clinical symptoms of esophageal reflux will have P. D. measurements, biopsies for light and electron microscopy, and various accessments of clinical state in order to determine the usefulness of P. D. measurements as a diagnostic and prognostic clinical tool.